Molecular Mechanisms in Synaptic Vesicle Endocytosis and Recycling

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Presentation transcript:

Molecular Mechanisms in Synaptic Vesicle Endocytosis and Recycling Pietro De Camilli, Kohji Takei  Neuron  Volume 16, Issue 3, Pages 481-486 (March 1996) DOI: 10.1016/S0896-6273(00)80068-9

Figure 1 Diagram Illustrating Key Protein Components of Nerve Terminal Clathrin Coats and Their Putative Reciprocal Interactions Dynamin is not indicated (see Figure 2). Neuron 1996 16, 481-486DOI: (10.1016/S0896-6273(00)80068-9)

Figure 2 Putative Role of Dynamin in Synaptic Vesicles Endocytosis Dynamin is recruited at clathrin coats (steps 1 and 2) via interactions with the adaptor AP2. Dynamin subsequenly assembles into a ring as soon an appropriate template forms: the neck of the invaginated bud (step 3). Ring formation is immediatly followed by GTP hydrolysis and fission (step 4). In the presence of GTPγS, the ring does not disassemble and several rings may pile up onto each other thus generating a narrow membrane tubule (step 5) (modified fromDe Camilli et al. 1995). Inset (A) shows an electron micrograph from the nerve ending of a cultured hippocampal neurons demonstrating presence of a dynamin ring (arrowhead) around the neck of a clathrin-coated bud. Prior to fixation, the neuron had been incubated with HRP-conjugated antibodies directed against the lumenal domain of synaptotagmin. Presence of HRP reaction product in the vesicle lumen demonstrates that the bud is involved in synaptic vesicles recycling. Inset (B) shows an electron micrograph from a lysed nerve terminal incubated with GTPγS as described by Takei et al. 1995a. Other micrographs by K. Takei, O. Mundigl, P. L. Daniell, and P. De Camilli. Neuron 1996 16, 481-486DOI: (10.1016/S0896-6273(00)80068-9)

Figure 3 Alternative Models of Synaptic Vesicles Recycling Model 1 proposes that after clathrin loss the endocytic vesicle fuses with an early endosomes from which a new synaptic vesicle is formed via a specialized budding reaction. Model 2 proposes that a new synaptic vesi- cle is generated directly from an uncoated clathrin-coated vesicle. Neuron 1996 16, 481-486DOI: (10.1016/S0896-6273(00)80068-9)